Coating gradient for lubricious coatings on balloon catheters

ABSTRACT

This invention relates to a dilatation balloon formed from an extruded tubular preform by blowing, said balloon having a body, at least one cone and at least one waist portion wherein said balloon has a lubricity coating gradient from the body portion which has the lowest coat thickness to the waist portion which has the highest coat thickness said coating applied to said extruded tubular preform prior to forming said balloon by blowing.

CROSS REFERENCE TO RELATED U.S. APPLICATIONS

This is a continuation in part of Application Ser. No. 08/868,301 filedJun. 3, 1997 now U.S. Pat. No. 5,902,631.

FIELD OF THE INVENTION

This invention relates to medical devices which have a segment which isinserted into the body and a segment which is retained outside the bodyfor manipulation. In particular, it relates to structures for which thein-the-body portion is a dilation balloon coated with a lubriciouscompound. Specifically, this invention relates to a method of coating aballoon which creates lubricity gradients on the balloon. The balloon iscoated prior to being blown and the resultant balloon has differentamounts of coating on the different parts of the balloon.

BACKGROUND OF THE INVENTION

Dilatation catheters are devices which have an inflatable balloon at thedistal end and are utilized in medical procedures such as angioplasty toeliminate stenoses or blockages. The balloons are inserted into vesselsin the body to open stenoses or blockages in the vascular system,usually by means of a catheter having a balloon at its distal end. Tothis end, the catheters may be inserted into a blood vessel, advancedthrough the blood vessel to a target site (i.e. the location of thestenosis or blockage) and the balloon is then inflated by supplying aliquid such as a radiopaque substance for angiography, through aninflation lumen. The inflation of the balloon causes stretching andexpansion of the target site, i.e. a blood vessel, in order to eliminatethe stenosis or blockage thereby reestablishing acceptable blood flow.

There are various types of catheters having single or multiple lumen,and some which are over-the-wire and some which are not. For the purposeof the present invention, all catheters will hereinafter be referred toas “balloon catheters.”

These devices need a certain degree of lubricity so as to avoid injuryto tissues, mucous membranes and other bodily parts with which they comeinto contact during insertion into a blood vessel, for instance.Balloons are typically made of polymeric materials including nylon,Selar®, polyether-polyester block copolymers (e.g. Hytrel® or Arnitel®),poly(amide-ether-ester) block copolymers such as Pebax®, polyethyleneterephthalate, polytetrafluoroethylene, polyvinyl chloride,polyurethanes, polyetherurethanes, polyesterurethanes, polyurethaneureas, polyurethane siloxane block copolymers, polyethylene,polypropylene or other similar extrudable thermoplastic, polymericmaterials, or composites thereof. Such materials are typicallyinherently non-lubricious making it necessary to add some type oflubricious coating to the surface in order to advance the device throughthe blood vessel more easily.

However, once the balloon is at the target site, it will be necessarythat it may be retained easily at the site during expansion orcontraction without slippage. This is more readily accomplished when theballoon material has no lubricity.

Balloons will therefore typically have a lubricating portion and anon-lubricating portion to avoid what is referred to in the industry asthe “watermelon seed” problem wherein a balloon which is too lubriciousshoots forward on inflation causing accidental slippage from the targetsite. U.S. Pat. No. 5,503,631 to Onishi et al. discloses a vasodilatingcatheter balloon whose body has a lubricating portion and anon-lubricating portion. The lubricious property of the balloon iscreated by grafting a lubricious coating onto a non-lubricioussubstrate. Only the tapered portions on opposite ends of the balloonwere treated.

The present inventors have now found a simplistic method for coating aballoon prior to formation of the balloon which achieves a lubriciouscoating gradient necessary for the successful use of a balloon catheter.The balloon exhibits superior retention at the target site without the“watermelon seed” effect, and exhibits excellent lubricity duringinsertion into the body cavity.

SUMMARY OF THE INVENTION

The present invention relates to a dilatation balloon formed from anextruded tubing by blowing. The balloon has a body, at least one coneand at least one waist portion and a lubricity coating gradient from thebody portion which has the lowest coating thickness to the waist portionwhich has the highest coating thickness. The balloon material is firstextruded into a tubular form prior to balloon formation which isaccomplished by dry blowing the balloon material. The lubricious coatingis applied to the extruded tubing prior to blowing the balloon. It isthe different amounts of expansion which occur for the body, the coneand the waist which cause the lubricity gradient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a dilatation catheter that includes aninflated coated balloon of the present invention.

FIG. 2 is a cross sectional view of the tubing prior to blowing theballoon.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A dilatation balloon catheter of the present invention, illustratedgenerally at 10 in FIG. 1, includes an inflatable balloon 14 mounted atthe distal end of an elongated flexible shaft 12. Except as notedherein, catheter 10 is conventional in its construction, providing alumen communicating with the interior of the balloon 14, for inflationand deflation of the balloon, and other optional features conventionalin the dilatation catheter art. The balloon 10, has an inflatedconfiguration, illustrated in FIG. 1 and is made up of three mainportions: the body 14, the cones 26 and the waist portions 28. FIG. 1illustrates the coating gradient wherein the coating 15 on body 14 is ata lower coating thickness than the coating on cones 26 which is at alower coating thickness than the coating on the waist portions 28,thereby establishing a coating gradient.

FIG. 2 represents a cross-sectional view of the extruded tubing fromwhich the balloon is blown. The tubing comprises a wall 16 such asformed from Pebax® and a coating 13 disposed thereon.

The present invention involves a process for the coating of dilatationballoons which creates a gradient coating on the balloons, the body ofthe balloon having less of the lubricious coating than the cones whichhave less coating than the waist.

Balloons are typically made of thermoplastic polymeric materialsincluding general classes such as thermoplastic elastomers, i.e. blockcopolymers; homopolymers, copolymers and terpolymers of ethylene;homopolymers, copolymers and terpolymers of propylene; ethyleneα-olefins; polyesters; polyamides; polyurethanes; polycarbonates, vinylcopolymers; ionomer materials and so forth. More specifically, materialssuch as nylon, Selar®, polyether-polyester block copolymers (i.e.Hytrel®), Pebax®(polyether block amide copolymers), Surlyn®,polyethylene terephthalate, polytetrafluoroethylene, polyvinyl chloride,polyetherurethanes, polyesterurethanes, polyurethane ureas, polyurethanesiloxane block copolymers, silicone polycarbonate copolymers, ethylenevinyl acetate copolymers, acrylonitrile-butadiene-styrene copolymers;polyphenylene sulfides; copolyesters or other similar extrudablethermoplastic, polymeric materials, or composites thereof may beutilized in the present invention. Thermosetting materials such aspolyimides may also be utilized.

Balloon materials which are preferable to the present invention includepolyether block amides, such as Pebax® 7033 or 7233; polyester blockethers such as Arnitel® EM 40; polyethylene terephthalate; and nylon.The formation of catheter balloons made of block copolymer elastomerswhere the hard segments are polyester or polyamide and the soft segmentsare polyether, is discussed in U.S. Pat. No. 5,556,383 issued Sep. 17,1996 to Wang et al. incorporated by reference herein.

Balloon formation may be carried out in any conventional manner withconventional extrusion and blowing techniques, but basically there arethree major steps in the process which include extruding a tubularpreform, blow molding the balloon and annealing the balloon. Dependingon the balloon material employed, the preform may be axially stretchedbefore it is blown. Techniques for balloon formation are discussed inU.S. Pat. No. 4,490,421 to Levy and in U.S. Pat. No. 5,348,538 issuedSep. 20, 1994 to Wang et al.

The present invention involves applying the lubricity coatings to theballoon material when it is in the tubular form, prior to blowing theballoon. The coating is applied to the entire tube at a constant andconsistent coating thickness. If the balloon material is stretched, thecoating may be applied before or after the stretching.

The lubricity gradient is created by expansion of the various parts of aballoon to different sizes. The body of the balloon expands the mostwhile the waist expands only slightly if at all and the cones exhibit anintermediate expansion. The balloon body, for instance, may expand to4-8 times the size of the tubular preform, while the waist may expandonly slightly or remain about the same size, during balloon formation.The expansion of the body creates more surface area while the amount ofcoating remains the same thereby reducing the coating thickness per unitarea on the body to a much greater degree than the reduction in coatingthickness on either the body or the waist.

The present inventors have found that by applying the lubricious coatingprior to balloon formation, the coating thickness on the body, whichexpands more, will be lower while the waist has a relatively highercoating thickness. The thickness on the cone varies inversely inaccordance with the ratio of expansion along the length thereof. Sincethe coating thickness will vary in accordance with the same factorswhich affect wall thickness variability, the ratio of coating thicknessto balloon wall material thickness will be approximately constant alongthe length of the balloon. In other words, the coating thickness on theballoon will be proportional to the thickness of the balloon wall afterblowing. The thinner the balloon wall, the thinner the coating. Thecoating thickness after blowing, may be controlled by the thickness ofthe coating applied to the tubular form.

The present inventors have found that the lubricious coatings usefulherein include any hydrophilic compound or any low friction hydrophobiccoating which imparts lubricity to the balloon material. The method ofthe present invention for forming lubricity gradients on the balloonitself, is not dependent on the coating utilized. The lubricity gradientcoating is a result of the method utilized to apply the coating ratherthan having any dependence on the type of coating utilized. Of course,some coatings are more desirable than others.

This lubricity gradient is desirable to prevent the “watermelon seed”effect. If the body of the balloon is too lubricious, the balloon mayslip from the target site when the liquid used for balloon expansion isinjected through the inflation lumen of the catheter, and into theballoon. It is critical to operations where balloon catheters areutilized, such as angioplasty, that the operator, usually the physician,is able to accurately and precisely position the balloon in the blockedvessel to create or expand the channel to restore acceptable levels ofblood flowing through the vessel.

If the body of the balloon has an insufficient amount of lubriciouscoating, the introduction of the uninflated balloon into the body willbe more difficult due to the higher friction between the balloon and thepatient's tissue or blood vessels.

In contrast, for stent delivery, it may be desirable to have lesslubrication on the balloon body than on the cones to prevent stentslippage from the target site.

The present method of coating catheter balloons has been found toproduce balloons which are readily retained at target sites, yet haveenough lubricity to be easily inserted into the vessels of patientswithout excessive discomfort.

Any hydrophobic or hydrophilic compound that imparts lubricity may beutilized in the coating method of the present invention. Examples ofuseful hydrophobic coatings include silicone lubricants or polymers andfluoropolymer coatings.

There are many hydrophilic compounds that may be utilized in the presentinvention. The water soluble lubricants useful herein includepolyalkylene glycols, alkoxy polyalkylene glycols, homopolymers andcopolymers of (meth) acrylic acid, copolymers of methylvinyl ether andmaleic acid, poly(vinylpyrrolidone) homopolymers, copolymers of vinylpyrrolidone, poly(N-alkylacrylamide), poly(vinyl alcohol),poly(ethyleneimine), polyamides, methyl cellulose,carboxymethylcellulose, polyvinylsulfonic acid, heparin, dextran,modified dextran, chondroitin sulphate and lecithin. The polymers aretypically chain-structured, non-crosslinked and water soluble having ahydrophilic group such as —OH, —CONH₂, —COOH, —NH₂, —COO—, —SO₃, —NR₃ ⁺and so forth where R is alkyl or hydrogen.

Derivatives of these polymers may also be utilized providing, even ifthey are not water soluble, that they are still of a structure which iscapable of being hydrated, or is dispersible in water. Examples includeesterified polymers, salts, amides, anhydrides, halides, ethers,hydrolyzates, acetals, formals, alkylols, quaternary polymers, diazos,hydrazides, sulfonates, nitrates, and ion complexes which are obtainedby condensation, addition, substitution, oxidation, or reductionreactions of the above mentioned water soluble polymers. Also useful arepolymers crosslinked with substances having more than one reactivefunctional group such as diazonium, azide isocyanate, acid chloride,acid anhydride, imino carbonate, amino, carboxyl, epoxy, hydroxyl andaldehyde groups. Further polymers include those copolymerized withvinyl, acrylic acid, methacrylic acid, diene compounds, and so forth.

The polyalkylene glycols or alkoxy polyalkylene glycols have thefollowing general formula:

R₁ and R₂ may be the same or different and can be H or an alkyl grouphaving 1 to about 6 carbon atoms, x is from 2 to about 500; and y isfrom 0 to about 100.

The polyalkylene glycols and alkoxy polyalkylene glycols may alsocontain functional groups such as, for example, hydroxyl, sulfur,nitrogen or oxygen.

Hydrophilic lubricants are beneficial because they will quickly swell inhe blood stream.

In a preferred embodiment of the present invention, the hydrophiliccoating is based on a maleic anhydride copolymer. Examples of suchcopolymers include poly(ethylene-maleic anhydride) sold by AldrichChemical Co. maleic anhydride-methyl vinyl ether copolymers such asGantrez® AN 169 sold by G.A.F. Corporation. With such a coating materialthe lubricity may be altered by differential hydrolysis of the anhydridegroups of the polymer and neutralization of the resulting acid groups.This may be readily accomplished by using a high pH solution (pH about10 or higher, suitably 10-12) using a gradual drawing, successivedipping or other technique as described above.

Another way the maleic anhydride copolymer may be modified is by partialreaction with a solution containing an anhydride or carboxylic acidreactive compound such as an amine, alcohol, epoxy or imine compound.The reactive compound may suitably be a low molecular weightmonofunctional compound, in which case hydrophilicity will usually bereduced. Polyfunctional compounds which produce surface crosslinking mayalso be employed. Polyethylene glycols or monohydroxy derivativesthereof may also be employed. Treatment of the coating with suchreactive compounds may be combined with neutralization reactions ofunreacted acid groups also obtained from the specific reactions or fromhydrolysis of any unreacted anhydride groups remaining after suchreactions.

Carboxylic acid-containing polymers may also be used as coatingmaterials in the invention. Copolymers of acrylic acid, methacrylicacid, maleic acid, fumaric acid or other polymerizable ethylenicallyunsaturated acids are examples.

In another embodiment, a hydrogel coating is provided with a lubricitygradient. For example polyethylene oxide may be captured in aninterpenetrating crosslinked acrylic polymer network by polymerizing amixture of an acrylic monomer composition comprising a monomer havingplural (meth)acrylate groups and polyethylene oxide, thereby providing ahydrogel coating.

In general hydrophilic lubricious coating materials are preferred ascoating materials for use in the invention. However hydrophobiclubricious coating materials can be similarly provided with a gradientof lubricity and thus employed in the invention. Additional examples ofpreferable hydrophilic coating materials include the homopolymers andcopolymers of vinyl pyrrolidone; polyacrylamides; polyethylene oxides;polyvinyl alcohols; (meth) acrylic acid homopolymers and copolymers;ionomeric polymers; collagen; polycarboxylic acids and so forth (whichmay optionally be mixed with polyurethane).

The coating compositions of the present invention may be coated out of asolvent or a cosolvent mixture using any conventional coating techniquessuch as dipping, spraying, brushing, and so forth. A preferable methodfor coating is dipping the tubular preform into the solution.

Useful solvents include alcohols, aliphatic hydrocarbons, aromatichydrocarbons, chlorinated solvents, esters, glycols, glycol ethers,ketones, and so forth. Polar solvents include alcohols, glycols, waterand so forth. Specific examples include ethanol, methanol, isopropanol,stearyl alcohol, ethylene glycol, propylene glycol, glycerin, water andso forth. Non-polar solvents include aliphatic hydrocarbons such asheptane and hexane; aromatic hydrocarbons such as toluene and xylene;chlorinated hydrocarbons such as perchloroethylene, methylene chloride,chloroform, carbon tetrachloride, 1,1,1-trichloroethane; fluorocarbons;mineral spirits and so forth.

For hydrophilic coatings, the preferable solvents are more polar andpreferably include the alcohols such as isopropyl alcohol or isopropanoland water and mixtures thereof. A 1-20% solution of lubricious polymeris preferably utilized and more preferably a solution of about 3% toabout 10 wt-% of the polymer is used.

The coating thickness, once the solvent has evaporated, is preferablyfrom about 1 to about 10 μm, more preferably from about 2 to about 6 μmand most preferably from about 2 to about 4 μm. The solvent may beallowed to evaporate at ambient temperatures or the tubing may be dried.

The tubular preform may then be blown into a balloon using any standardblowing techniques. The coating thickness, after blowing, will vary fromthe lowest coating thickness on the body portion of the balloon, tohigher coating thickness on the cones and even higher coating thicknesson the waist. For instance, the thickness on the balloon body may befrom about 0.2 μm to about 1 μm, preferably from about 0.3 μm to about0.8 μm, while that on the cones or waist may be from about 1 μm to about10 μm, preferably from about 2 μm to about 6 μm.

The coefficients of static friction vary depending on the coatingthickness and will preferably be less on the cone and waist portionsthan on the body portion.

The preferable hydrophilic coating materials have been found to exhibitexcellent adhesion to the balloon material.

The following non-limiting examples further illustrate the coatingmethod of the present invention.

EXAMPLES Example 1

Pebax® tubing segments of conventional dimension for a 3 mm angioplastyballoon were coated with a hydrophilic coating of a 10% solution ofpoly(ethylene maleic acid). The tubing segments were dried at 85° C. for2 hrs. The coating thickness applied was 2-4 micrometers (μm).

The coated tubing segments were blown into a 3 mm balloon.

Coating thickness on the balloon body portion was 0.3-0.6 μm while onthe cones it became thicker and on the waist it stayed nearly the sameas the original dried coating thickness (2-4 microns). The coefficientsof static friction on the balloons body portions were 0.141-0.168,whereas for waist portions they were 0.035-0.065.

Example 2

Pebax® tubing is coated with a hydrophilic coating of a 3-10% solutionof polyvinylpyrrodlidone (PVP) in a mixed IPA/water (80/20 ratio)solvent. The tubing is dried at about 85° C. for 2 hrs to removesolvent. The coated tubing is blown into balloons at a temperature ofabout 95° C. The coating gives the balloons a different lubricitybetween the body and waist portions.

Example 3

Pebax tubing segments were coated with hydrophilic coating using a 5%solution of polyethylene oxide in a mixed IPA/water (80/20 ratio)solvent and a 5% solution of diacrylate monomers in IPA with apolymerization initiator. The tubing was dried at about 90° C. for 3hours, or under UV-light for 45 seconds. The coated tubing was blowninto balloons at about 95° C. The coating thickness on the balloonbodies was 0.15-0.30 microns, on cones it was about 1-2 microns.

Example 4

Pebax tubing segments were coated with hydrophilic coating of 3%solution of acrylamide in mixed IPA/water solvent. The coated tubingsegments were dried at 90° C. for 3 hours and then blown into balloons.A large difference between the lubricity of the body and cones of theballoons was obtained.

Example 5

Balloons made of Pebax material are coated with a hydrophilic coating byspraying the body and cone portions for different time periods with a3-5% solution of polyvinylpyrrolidone in IPA/water. The coated balloonsare dried at 50° C. for 6 hours.

The coating thickness varied on the body cones according to thedifferent spray times used.

Example 6

Pebax tubing segments were coated of a 2% solution of silicon liquids,Dow Corning DC-360 and MDX-4 (relative weight ratio 2:1), in heptane.The coatings were dried at 50° C. and RH 50% for 4 hours. The coatedtubing segments were blown into balloons at 95° C. The coating thicknessand lubricity was different on the body and waist portions of theballoons.

Those skilled in the art may recognize other equivalents to the specificembodiments described herein which equivalents are intended to beencompassed by the claims attached hereto.

What is claimed is:
 1. A dilatation balloon formed from an extrudedtubular preform by blowing, said balloon having a body, at least onecone and at least one waist portion wherein said balloon has a lubricitycoating with a gradient of thickness from the body portion which has thelowest coating thickness to the waist portion which has the highestcoating thickness.
 2. The dilatation balloon of claim 1 wherein saidlubricity coating is applied to said tubular preform before blowing. 3.The dilatation balloon of claim 1 wherein said lubricity coatingcomprises at least one copolymer of maleic acid.
 4. The dilatationballoon of claim 3 wherein said copolymer of maleic acid is obtainedfrom maleic anhydride copolymer modified by reaction of some of theanhydride groups thereof with a member selected from the groupconsisting of monofunctional amines, alcohols, epoxies, imines andmixtures thereof.
 5. The dilatation balloon of claim 4 wherein saidcopolymer of maleic anhydride is selected from the group consisting ofpoly(ethylene-maleic anhydride) copolymer and maleic anhydride-methylvinyl ether copolymer.
 6. The dilatation balloon of claim 1 wherein saidlubricity coating comprises a hydrogel polymer.
 7. The dilatationballoon of claim 6 wherein said hydrogel polymer comprises polyethyleneoxide captured in an interpenetrating crosslinked acrylic polymernetwork.
 8. The dilatation balloon of claim 1 wherein said lubricitycoating comprises at least one polycarboxylic acid.
 9. The dilatationballoon of claim 1 wherein said lubricity coating comprises a(meth)acrylic acid homopolymer or copolymer.
 10. The dilatation balloonof claim 1 wherein said lubricity coating comprises a vinyl pyrrolidonehomopolymer or copolymer.
 11. The dilatation balloon of claim 1 whereinsaid lubricity coating gradient is created by expansion of a segment ofpolymer tubing coated with a uniform coating of said lubricity coatingso as to form said balloon with differently sized waist, cone and bodyportions.
 12. The dilatation balloon of claim 11 wherein said coatedtubing is dried at a temperature of from about 50° C. to about 90° C.prior to said expansion.
 13. The dilatation balloon of claim 1 whereinsaid lubricity coating is selected from the group consisting ofhydrophobic polymers and hydrophilic polymers.
 14. A catheter havingmounted thereon a dilatation balloon of claim 1.